In term of new case per year, prostate cancer (PC) is currently ranked among the most frequent malignancy and is one of the major causes of cancer-related mortality, fourth after lung cancer, colorectal cancer and breast cancer. (1) Prostate-specific antigen (PSA) and digital rectal examination (DRE) are the main screening tools for prostate cancer screening. (2) PSA testing with or without DRE is a proposed screening strategy in order to diagnose PC in an early localized stage for which a curative treatment is possible. (2) To evaluate the efficacy of PC screening, two large randomized trials have been published. (3). The European Randomized Study of Screening for Prostate Cancer in Europe (ERSPC trial) included a total of 162,243 men between 55 and 69 years of age. The men were randomly assigned to a group offered PSA screening at an average of once every 4 years or to an unscreened control group. During a median follow-up of 9 years, the cumulative incidence of PC was 8.2% in the screened group and 4.8% in the control group. The absolute risk difference was 0.71 deaths per 1000 men. The ERSPC investigators concluded in this study that PSA-based screening reduced the rate of death from PC by 20%. (4) A second trial, the Prostate, Lung, Colorectal, and Ovary (PLCO) trial in the United States was published. The PLCO cancer screening trial randomly assigned 76,693 men to receive either annual screening with prostate-specific antigen (PSA) and digital rectal examination (DRE) or standard care as the control (after a follow-up of 7 years, the incidence of PC per 10,000 person-years was 116 (282 cancers) in the screening group and 95 (232.2 cancers) in the control group (rate ratio: 1.22). The incidence of death per 10,000 person-years were 2.0 (50 deaths) in the screened group and 1.7 (44 deaths) in the control group (rate ratio: 1.13). The PLCO project team concluded that PC-related mortality in screen-detected individuals was very low and not significantly different between the two study groups. (5). The PLCO trial will probably never be able to answer whether or not PSA and DRE screening can influence PC mortality, one likely explanation being the follow up time 7 years that was short compared to the European trial and the sensitivity and specificity of the tests used. Based on this last result, the US preventive services task force (USPSTF) recently issued a recommendation against the use of prostate-specific antigen (PSA) testing for prostate cancer screening. (6) The level of PSA is used as continuous parameter, the higher the value, the more likely the existence of PC. The finding that many men may have PC, despite low levels of serum PSA, has been underscored by recent results from a US prevention study. (7) In a prospective multicentre trial, PC was found on biopsy in 56% of men with a free/total (f/t) PSA<0.10 but in only 8% of men with a f/t PSA>0.25. (8) These data were confirmed in a recent screening test including 27,730 men with a serum PSA concentration between 2.1 and 10 ng/ml. (9) Several pre-analytical and clinical factors may influence the free/total PSA, for example, free PSA is unstable at both 4° C. and at room temperature. For this reason it is urgent to have strong, accurate, sensitive and specific non-invasive test for PC Moreover, the global market for cancer diagnosis is booming since life expectancy is increasing. In developed countries, the percentage of the population older than 60 years was estimated in 2000 to rise from 16.1% in 2000 to 21.4% in 2010. In 2000, the world diagnosis market represented sales of nearly $620 million, with the United States alone accounting for $150 million (www.cowen.com/Research.asp). Implementation of policies for annual screening, age-appropriate cancer screening will revolutionize this market even already many health authorities such as Medicare provide already coverage for an annual PSA test for all men age 50 and older (www.medicare.gov/default.aspx).